3 The mortality rate for acute liver failure ranges between 56% and 80%

4 Abnormal LFT is NOT ALF Dear DoctorPatient’s bilirubin is 600 and has liver failure- kindly urgently seeFamily was told transplant may be necessary

5 Formal diagnosis of acute liver failureAn increase in PT by 4-6 seconds (INR>1.5)And the development of hepatic encephalopathy (HE).In a patient without pre-existing cirrhosis and with an illness of less than six months duration.

6 UK incidence of cirrhosis 17 per 100,000Prevalence of cirrhosis is 76 per 100,000ALF incidence is 1-6 per million per year

27 Classification of HRSType I is defined by a rise in creatinine level to over 221 micromoles/L in less than 2 weeksMedian survival of 2 weeksType II is defined as less severe renal insufficiency; it is principally characterized by ascites that is resistant to diuretics.Median survival of 3-6 months.

28 Vasoactive Medical treatmentTerlipressin bolus(0.5mg/4h)-increase every 3 days if no response to 1-2mg/4hGiven until creatinine normalizes or for 15 daysAlbumin 1g/kg on day1( one bag of HAS contains 20grams)20-60g/d thereafter

32 The pathophysiology of HEA large body of work points at ammonia as a key factor in the pathogenesis of HE.Portal ammonia is derived from both the urease activity of colonic bacteria and the deamidation of glutamine in the small bowel.The intact liver clears almost all of the portal vein ammonia, converting it into glutamine and preventing entry into the systemic circulation.Ammonia- astrocyte swelling in brain

33 Patients with grade II HE should be managed in a HDU environment.Grades III and IV HE requires definitive airway protection and appropriate monitoring.Grade IV HE is strongly associated with elevated levels of serum ammonia, a high incidence of raised intracranial pressure and the development of uncal herniation.

35 In acute and chronic liver disease, increased arterial levels of ammonia are commonly seen.However, correlation of blood levels with mental state in cirrhosis is inaccurate.

36 Lactulose is a first-line pharmacological treatment of HE.Lactulose – reaches colon, where bacteria will metabolize the lactulose to acetic acid and lactic acid.This lowers the colonic pHformation of the non-absorbable NH4+ from NH3,Other effects like catharsis also contribute to the clinical effectiveness of lactulose.

39 The coagulopathy of liver diseaseFailure to produce clotting factors II, V, VII and IXFailure of the diseased liver to clear activated clotting factors.Degree of hypersplenism and thrombocytopaenia often adds to the coagulopathy, especially if disseminated intravascular coagulation (dic) also co-exists.The degree of coagulopathy is a measure of severity of liver disease and of patient prognosis.Routine correction of coaguloapthy is therefore NOT indicated unless active bleeding or planned interventions require it

40 Sepsis Infection may be the initiating event of liver failure,Intercurrent sepsis is also a common problem .Impaired immune function, in part secondary to reduced complement factor production andImpaired neutrophil, leukocyte and monocyte function, can result in delayed presentation of clinical signs of infection.The interventions required for diagnosis and management of liver disease also increase patient vulnerability to invasive infection.

41 Role of prophylactic antibioticOnly patients who have an episode of gastrointestinal bleedingor an episode of spontaneous bacterial peritonitis (SBP) have been shown to have a significant outcome benefit from prophylactic antibiotics.

42 In presence of sepsisChoice of antibiotic should be guided by local microbiological surveillance.The high incidence of mycoses - low threshold for antifungal.Regular microbiological surveillance

43 Role of NAC Efficacy of NAC is well established in PCM induced ALFNon PCM ALF – role of NAC is controversial175 patients of non PCM ALF received NACTransplant free survival at 3 weeks was 52% in NAC group compared to 30% in placebo arm ( only with coma grade of 1-2)United States ALF study group- overall was 70% vs 66%

46 ELAD Both reduce the level of bilirubin, bile salt ammonia etcHowever no of patients dying or requiring liver transplant did not improveDevices remain experimental and large-scale phase two and three trials are awaited

47 Summary• The mortality rate for acute liver failure ranges between 56% and 80%• The main role of intensive care therapy is multi-organ support• The commonest cause of acute liver failure in the western world is paracetamol toxicity• Hepatic encephalopathy is no longer the main cause of death but it’s detection and management requires sophisticated cardiovascular and cerebral monitoring• Hepatorenal failure is due to the complex interplay between splanchnic, renal and systemic circulatory responses to liver failure. Terlipressin has been shown to be of use in its treatment• Novel hepatic replacement therapies are under development but definitive studies as to their efficacy are, as yet, unpublished.